8-55161765-C-A

Variant names:

• chr8-55161765-C-A
• rs7837220
• NM_052898.2:c.806+58471C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052898.2(XKR4):​c.806+58471C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 369,834 control chromosomes in the GnomAD database, including 16,482 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.32 (8577 hom., cov: 32)
  • Exomes 𝑓: 0.26 (7905 hom.)
• Consequence: XKR4 NM_052898.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.632
• Publications: 1 publications found

Genes affected

XKR4 (HGNC:29394): (XK related 4) Enables phospholipid scramblase activity. Involved in phosphatidylserine exposure on apoptotic cell surface. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000253857 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052898.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XKR4	NM_052898.2	MANE Select	c.806+58471C>A		intron	N/A	NP_443130.1
	LOC105375844	NR_188097.1		n.190+121C>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XKR4	ENST00000327381.7	TSL:1 MANE Select	c.806+58471C>A		intron	N/A	ENSP00000328326.5
	ENSG00000253857	ENST00000522559.2	TSL:2	n.206+121C>A		intron	N/A
	ENSG00000253857	ENST00000668329.2		n.217+121C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48990 AN: 151970 Hom.: 8563 Cov.: 32

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.313

GnomAD4 exome AF: 0.262 AC: 57050 AN: 217746 Hom.: 7905 AF XY: 0.261 AC XY: 31713 AN XY: 121396

African (AFR) AF: 0.467 AC: 2609 AN: 5586

American (AMR) AF: 0.224 AC: 3285 AN: 14662

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1551 AN: 5196

East Asian (EAS) AF: 0.273 AC: 2133 AN: 7802

South Asian (SAS) AF: 0.245 AC: 11010 AN: 44966

European-Finnish (FIN) AF: 0.251 AC: 2308 AN: 9180

Middle Eastern (MID) AF: 0.349 AC: 537 AN: 1538

European-Non Finnish (NFE) AF: 0.260 AC: 30767 AN: 118404

Other (OTH) AF: 0.274 AC: 2850 AN: 10412

GnomAD4 genome AF: 0.322 AC: 49032 AN: 152088 Hom.: 8577 Cov.: 32 AF XY: 0.323 AC XY: 24043 AN XY: 74358

African (AFR) AF: 0.472 AC: 19568 AN: 41456

American (AMR) AF: 0.271 AC: 4145 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1025 AN: 3468

East Asian (EAS) AF: 0.277 AC: 1431 AN: 5166

South Asian (SAS) AF: 0.238 AC: 1150 AN: 4822

European-Finnish (FIN) AF: 0.269 AC: 2845 AN: 10578

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17839 AN: 67984

Other (OTH) AF: 0.312 AC: 660 AN: 2116

Alfa AF: 0.200 Hom.: 628

Bravo AF: 0.332

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.69
DANN	Benign	0.74
PhyloP100		-0.63
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7837220; hg19: chr8-56074325;